A Systematic Review of the Cost-Effectiveness Evaluation of Tisagenlecleucel for the Treatment of Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Pediatric and Young Adult Populations
Introduction/Background/Significance: Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) presents a major clinical challenge, particularly in pediatric and young adult populations. While first-line treatments achieve high initial remission rates, recurrence or treatment resistance is associated with poor outcomes and limited therapeutic alternatives1. Chimeric antigen receptor T-cell (CAR-T) therapies have emerged as transformative options in hematologic malignancies, offering targeted mechanisms of action. Tisagenlecleucel, a CD19-directed autologous CAR-T cell therapy, has shown significant clinical efficacy and received regulatory approval for use in R/R B-ALL. However, its high acquisition cost raises concerns about its cost-effectiveness in different health system contexts2. As economic evaluation becomes increasingly essential in guiding the adoption of high-cost therapies, this systematic review aims to assess the cost-effectiveness of Tisagenlecleucel compared to conventional salvage chemotherapy in pediatric and young adult patients with R/R B-ALL.
Materials and Methods/Case Presentation/Objective: This systematic review was conducted in accordance with PRISMA guidelines and was registered in the PROSPERO database (CRD42021266998). A comprehensive search was performed in January 2022 using MEDLINE via PubMed, EMBASE, LILACS, Cochrane CENTRAL, and Web of Science. Two independent reviewers screened titles and abstracts, followed by full-text review, using predefined inclusion criteria focused on cost-effectiveness analyses comparing Tisagenlecleucel to conventional therapies in the target population.
Results/Description/Main Outcome Measures: A total of 5,627 records were identified, of which six studies met all eligibility criteria and were included for qualitative synthesis. The comparator treatments varied across studies and included Blinatumomab (Blina), Clofarabine monotherapy (Clo-M), Clofarabine combined with Cyclophosphamide and Etoposide (Clo-C), and the combination of Fludarabine, Cytarabine, and Idarubicin (FLA-IDA). All studies reported that Tisagenlecleucel offered improved clinical outcomes. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for Tisagenlecleucel ranged from $25,569 (vs. Blina) to $38,837 (vs. Clo-C), remaining well below the commonly cited U.S. willingness-to-pay threshold of $100,000/QALY. However, Tisagenlecleucel's upfront drug cost was substantially higher—approximately 4.3 times, 10.8 times, and 4.7 times greater than Clo-M, Clo-C, and Blina, respectively.
Conclusions: Although significantly more expensive in absolute terms, Tisagenlecleucel demonstrated favorable cost-effectiveness in all reviewed studies due to its superior clinical efficacy and long-term health benefits. The findings support its consideration as a valuable treatment option for pediatric and young adult patients with R/R B-ALL. Nonetheless, further real-world economic evaluations are needed to understand its budgetary impact, particularly in resource-limited settings and low- and middle-income countries.
Trademarked Items
CAR-T; Acute lymphoblastic leukemia; Cost-effectiveness analysis; Tisagenlecleucel.
References
1.Maude SL, Laetsch TW, Buechner J, et al: Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia.NEngl JMed 378:439-448, 2018. https://doi.org/10.1056/NEJMoa1709866 2.Bach PB, Giralt SA, Saltz LB: FDA approval of tisagenlecleucel: Promise and complexities of a $475000 cancer drug. JAMA 318:1861-1862, 2017. https://doi.org/10.1001/jama.2017.15218
